scholarly journals Low temperature exerts protective effects by inhibiting mitochondria-mediated apoptosis pathway following pressure injury to rat muscle

2021 ◽  
Vol 55 ◽  
Author(s):  
Wenyu Zhang ◽  
Ran Miao ◽  
Jingping Tang ◽  
Qingqing Su ◽  
Peifeng Li ◽  
...  
Keyword(s):  
Low Temperature ◽  
Tissue Damage ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Caspase 9 ◽  
Time Points ◽  
Temperature Range ◽  
Muscle Tissues ◽  
Pressure Injury ◽  
Injury Control

ABSTRACT Objective: We aimed to determine the effect of different low-temperature range interventions at different time-points in a rat model of pressure injury (PI) produced by Ischemia/Reperfusion (I/R) injury. Methods: Sprague-Dawley rats were randomly assigned to blank control, injury control, and temperature intervention groups. Rats in the injury control and temperature intervention groups (involving exposure to different temperature range at different time-points) were subjected to three cycles of I/R injury with 2-h ischemia and 0.5-h reperfusion to induce PI. Results: The muscle tissues exhibited degenerative changes after compression. Low temperature intervention of 16–18°C in the ischemia period resulted in the lowest degree of tissue damage and significantly decreased levels of Bcl-2-associated X protein (Bax), caspase-9, and caspase-3. Moreover, it resulted in the highest expression level of B-cell lymphoma 2 (Bcl-2) and lowest expression levels of Bax, caspase-9, and caspase-3 in muscle tissues among all intervention groups. Conclusion: Low-temperature intervention at 16–18°C during the ischemia period showed optimal effects on the expressions of apoptotic factors during the development of PI with I/R-induced tissue damage.

Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis

2020 ◽  
Vol 20 (4) ◽  
pp. 504-517
Author(s):  
Yu-Lan Li ◽  
Xin-Li Gan ◽  
Rong-Ping Zhu ◽  
Xuehong Wang ◽  
Duan-Fang Liao ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cell ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Caspase 9

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

scholarly journals Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Tsen-Ni Tsai ◽  
Jia-Jing Ho ◽  
Maw-Shung Liu ◽  
Tzu-Ying Lee ◽  
Mei-Chin Lu ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Caspase 3 ◽  
Cecal Ligation ◽  
B Cell Lymphoma ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Glutamate Pyruvate ◽  
Serum Glutamate

This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.

scholarly journals Small-molecule XIAP antagonist restores caspase-9–mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 369-375 ◽  
Author(s):  
Saskia A. G. M. Cillessen ◽  
John C. Reed ◽  
Kate Welsh ◽  
Clemencia Pinilla ◽  
Richard Houghten ◽  
...  
Keyword(s):  
B Cell ◽  
Small Molecule ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Caspase 9 ◽  
Lymphoma Cells ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Apoptosis Protein ◽  
Large B Cell

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.

Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12

2020 ◽  
Vol 39 (6) ◽  
pp. 797-807 ◽  
Author(s):  
W Wang ◽  
L Huang ◽  
Y Hu ◽  
ER Thomas ◽  
X Li
Keyword(s):  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Water Soluble ◽  
Caspase 9 ◽  
Neuroprotective Effects ◽  
Adrenal Chromaffin Cell ◽  
Chinese Medicines ◽  
Apoptotic Effect ◽  
Thioredoxin 1 ◽  
Adrenal Chromaffin

Acrylamide (ACR) is a water-soluble chemical that is commonly used in chemical and cosmetic manufacture. Many studies have been carried out to investigate the neurotoxicity mechanisms of ACR, resulting in oxidative stress and nerve damages. One of the commonly used traditional Chinese medicines is notoginsenoside R1 (NR1). However, its mitochondrial-mediated apoptotic effect caused in ACR-induced neurotoxicity has not been reported. Our results have shown that NR1 resisted the neurotoxicity induced by ACR by upregulating the levels of thioredoxin-1 (Trx-1) in Rat adrenal chromaffin cell tumor (PC12) cells. NR1 inhibited the increase in levels of Bax, caspase-9, and caspase-3, which was instigated by ACR. Moreover, NR1 inhibited the decrease in levels of B-cell lymphoma 2 and Trx-1 induced by ACR. The downregulation of Trx-1 aggravated the mitochondrial-mediated apoptosis and increased the expression of the above molecules, which was induced by ACR. In contrast, overexpression of Trx-1 attenuated the mitochondrial-mediated apoptosis and inhibited the expression of the mentioned molecules induced by ACR. Our results suggested that NR1 protected ACR-induced mitochondrial apoptosis by upregulating Trx-1.

scholarly journals Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

2021 ◽  
Vol 18 (7) ◽  
pp. 1385-1390
Author(s):  
Jiexiang Chen ◽  
Yong Cao ◽  
Yan Li ◽  
Li Tang ◽  
Xiaolan Yu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Cell Line ◽  
Proliferative Activity ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Gsk 3Β

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action. Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to determine the anti-proliferative activity of wogonoside (2 - 128 μM) on bladder cancer 5637 cell line at various times, and the halfmaximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, ip) against bladder cancer 5637 cell line was evaluated in nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting and enzyme-linked immunosorbent assay (ELISA) were carried out to investigate the levels of the caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X-protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT. Results: The in vitro results revealed that wogonoside exerted anti-proliferative activity against bladder cancer 5637 cells with an IC50 of 20.59 μM (p < 0.01), in a concentration- and time-dependent manner. Furthermore, wogonoside treatment also significantly suppressed tumor volume in mice (p < 0.01). The potential mechanisms were mainly associated with apoptosis mediated by mitochondria via upregulation of caspase-3, caspase-9, and Bax levels and down-regulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT. Conclusion: The results reveal that wogonoside has remarkable anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer.

scholarly journals Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chien-Ming Chu ◽  
Li-Chung Chiu ◽  
Chung-Chieh Yu ◽  
Li-Pang Chuang ◽  
Kuo-Chin Kao ◽  
...  
Keyword(s):  
Cell Death ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
B Cell Lymphoma ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.

scholarly journals Induction Effect and Underlying Mechanism of Scutellarin on Apoptosis of Human Colorectal Cancer SW480 Cells and AOM/DSS Mouse

2020 ◽  
Author(s):  
Sha Zeng ◽  
Li Tan ◽  
Hui Zhao ◽  
Han Yang ◽  
Li Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Mrna Levels ◽  
Human Colorectal Cancer ◽  
Caspase 9 ◽  
Bax Protein ◽  
Sw480 Cells

Abstract Background: This study was aimed to investigate the effect of Scutellarin on apoptosis of human colorectal cancer SW480 cells and azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse, and clarify its mechanism. Methods: 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and cell migration assay were performed to detect the viability and proliferation of SW480 cells that treated with different concentrations of Scutellarin. Hoechst33342 Staining to determine apoptosis, detecting Caspase-3 and Caspase-9 activities after administration of different concentrations of Scutellarin. AOM/DSS mouse were administrated with Scutellarin; immunohistochemistry and western blot was employed to detect the effect on the expression of BCL2-Associated X (Bax) and B-cell lymphoma-2 (Bcl-2) proteins, and the message Ribonucleic Acid (mRNA) levels of Bax, Bcl-2, Caspase-3and Caspase-9 were assessed with quantitative reverse transcription polymerase chain reaction (qRT-PCR). The data was analyzed by one-way analysis of variance (ANOVA) with SPSS19.0 software, expressed as mean ± standard deviation (x ± s). Results: Scutellarin could inhibit the proliferation of SW480 cells after treatment with different concentrations of Scutellarin, while the chromatin condensation and nucleus showed more intense blue fluorescence. Moreover, Scutellarin could significantly increase the activities of Caspase-3 and Caspase-9 as well as different concentrations of Scutellarin could significantly down-regulate the expression of apoptosis related protein Bcl-2 and up-regulate the expression of Bax protein. When compared with the solvent control group, the relative expression levels of the related gene Bcl-2 were down-regulated by different concentrations of Scutellarin, while the Bax, Caspase-3 and Caspase-9 genes were up-regulated. Conclusion: Scutellarin can inhibit the in vitro activity of colon cancer SW480 cells, promote Bax expression, inhibit Bcl-2 expression, and up-regulate the activities of apoptotic enzymes Caspase-3 and Caspase-9 to induce apoptosis in vivo and in vitro, suggesting that it has a certain therapeutic effect on colon cancer.

scholarly journals Polydeoxyribonucleotide Ameliorates Inflammation and Apoptosis in Achilles Tendon-Injury Rats

2020 ◽  
Vol 24 (Suppl 2) ◽  
pp. 79-87
Author(s):  
Jeong Ho Rho ◽  
Il-Gyu Ko ◽  
Jun-Jang Jin ◽  
Lakkyong Hwang ◽  
Sang-Hoon Kim ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Thermal Hyperalgesia ◽  
B Cell Lymphoma ◽  
Camp Response Element Binding ◽  
Tendon Injury ◽  
Good Effect ◽  
Caspase 9 ◽  
Tnf Α

Purpose: Adenosine A<sub>2A</sub> receptor agonist polydeoxyribonucleotide (PDRN) possesses an anti-inflammatory effect and suppress apoptotic cell death in several disorders. In this current study, the effect of PDRN on inflammation and apoptosis in rats with Achilles tendon injury was investigated.Methods: von Frey filament test and plantar test were conducted for the determination of pain threshold. Analysis of histological alterations was conducted by hematoxylin and eosin staining. Immunohistochemistry for cleaved caspase-3-positive cells and cleaved caspase-9-positive cells was done. Enzyme-linked immunoassay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and cyclic adenosine-3’,5’-monophosphate (cAMP). Western blot was conducted to detect the protein levels of cAMP response element-binding protein (CREB), protein kinase A (PKA), Bcl-2-associated X (Bax), and B-cell lymphoma 2 (Bcl-2).Results: PDRN treatment relieved mechanical allodynia and alleviated thermal hyperalgesia after Achilles tendon injury. TNF-α and IL-6 concentrations were decreased by PDRN application. PDRN injection significantly enhanced cAMP concentration and phosphorylated CREB versus CREB ratio, showing cAMP-PKA-CREB pathway was activated by PDRN application. PDRN treatment inhibited percentages of cleaved caspase-3-positive cells and caspase-9-posiive cells and the suppressed Bax versus Bcl-2 ratio in Achilles tendon injury rats.Conclusions: PDRN is probably believed to have a good effect on pain and inflammation in the urogenital organs. PDRN may be used as a new treatment for Achilles tendon injury.

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